Since their identification in 2005, T helper (Th)17 cells have been proposed to play important roles in several human diseases, including various autoimmune conditions, allergy, the development and progression of tumors, and the acceptance or rejection of transplanted organs and bone marrow. Focusing on human studies, here we review recent developments regarding Th17 biology and function in each of these fields. Th17 cells actively participate in the pathogenesis of autoimmune disease, allergy and transplantation rejection. Th17 cells contribute to protective antitumor immunity in human epithelial malignancy, whereas Th17-associated cytokines may also be associated with tumor initiation and growth in the context of chronic inflammation and infection. Also discussed is how the in vivo plasticity of Th17 cells may be an important feature of Th17 cell biology in human disease.